Continuing our studies on the influence of aging on brain energy and catecholamine metabolism, and its effect on homeostatic responses to stress, we propose to work on two major projects. Project 1 (a) continuation of work with decarboxylase inhibitors and L-DOPA supplementation, with the aim of identifying beneficial behavioral effects of compensating for brain dopamine deficiency in old rats. (b) Catecholamine changes in discrete brain regions and nuclei, in response to stress, will be compared in young and old animals, using the Palkovitz punch technique and micro-assays, in order to identify the sites of dopamine deficiency in old animals, and to relate this to behavioral changes with age. Project 2 Continuation of studies on brain energy metabolism will compare the effects of hemorrhagic hypotension plus hypoxia on rate of depletion of brain ATP and creatine phosphate, and rate of accumulation of lactate and pyruvate in young and old rats, and similar comparison of rate of restoration of normal brain metabolism during recovery. These items will be correlated with EEG changes, carotid blood flow, and brain oxygen tension profiles measured with oxygen micro-electrodes. In addition, in vitro studies will be made of brain mitochondria in young and old rats, under above conditions, emphasizing ADP:O ratios, respiratory control ratios, and presence or absence of uncoupling. $